Project for multiple sclerosis treatment wins Jorge Ruas Award
The project “AAV-Based Gene Therapy for PPMS”, which proposes an innovative therapy for a severe form of Multiple Sclerosis, has won the inaugural edition of the Jorge Ruas Award. The €100,000 prize was awarded as part of the Tecnimede Open Innovation Competition, an initiative by the Tecnimede Group in partnership with HiseedTech. The winning proposal was developed by a team consisting of i3S researchers (Matthew Holt, Joana Paes de Faria and Nanci Abreu), along with colleagues from the University of Cambridge (James Dooley).
The award-winning proposal describes a pioneering gene therapy for primary progressive multiple sclerosis (PPMS), an inflammatory brain disease for which no effective treatment currently exists. Globally, around 2.9 million people suffer from multiple sclerosis, and 10 to 15 percent are affected by PPMS — a condition marked by pain, loss of mobility, and often paralysis. “There is currently only one available therapy for this type of MS, and its effectiveness is very limited,” explains Matthew Holt.
The therapy developed by the winning team is the first to deliver an anti-inflammatory compound specifically into the brain, with the aim of reducing chronic inflammation in a controlled and reversible manner. This is possible due to the recent discovery of regulatory T cells (Tregs) in the brain, immune cells which help reduce inflammation and promote tissue repair. However, these cells rely on a substance called Interleukin-2 (IL-2) to survive, and IL-2 levels are actually very low in the normal brain, meaning only a small Treg population is usually present. The team’s strategy for treating PPMS is to increase the number of these Tregs in the brain so they can better fight inflammation.
To achieve this, the team developed an innovative (and patented) three-stage system: First, they use a harmless, genetically modified virus to deliver the gene encoding IL-2 across the blood-brain barrier and into the brain; Once in the brain, the virus causes astrocytes (a type of brain cell) to start producing IL-2; To ensure this process only happens when desired, it is activated only in the presence of a safe drug called minocycline, which acts as a “safety switch”.
Using this virus-based system, Paes de Faria notes, “we were able to significantly slow disease progression in an animal model of multiple sclerosis, even with a low dose of the treatment. This shows that tackling inflammation directly in the brain — the right place, at the right time, with the right molecule — can be extremely effective.”
Diseases of the central nervous system (CNS), Holt explains, “are extremely difficult to treat because the blood-brain barrier blocks most drugs and biological agents from entering the brain after peripheral administration. Ten years ago, my lab began developing innovative viral-based delivery systems that could cross the BBB to deliver therapies. However, developing our anti-inflammatory treatment for PPMS was only possible due to the productive collaboration we enjoy with top immunologists - James Dooley and Adrian Liston in Cambridge."
Holt notes that “beyond multiple sclerosis, the technology also has potential to treat a range of brain diseases, including neurodegenerative conditions typically associated with aging”, as his team have also managed to deliver antibodies targeting key proteins involved in Alzheimer’s disease and demonstrated disease-modifying effects in Alzheimer’s mouse models.
With the financial support and collaboration of the Tecnimede Group, the team now aims to move forward to test the safety and efficacy of their IL-2 system in non-human primates — a crucial step before beginning clinical trials in humans. “Our goal is to validate the scientific foundations of the work and, within three years, be ready to launch the first clinical trials for PPMS”, says the neuroscientist.
For the i3S researcher, “it is extremely rewarding to see the transformative potential of our system recognised by Tecnimede through the Jorge Ruas Award.” This prize, he adds, “also represents recognition of the contributions and hard work of all the talented scientists I’ve had the privilege of collaborating with throughout this journey, as well as the generous support of our funders.”
About the Jorge Ruas Award
Created in partnership with HiseedTech, the Jorge Ruas Award aims to recognise and fund innovative projects with the potential to transform the pharmaceutical industry. It honours the vision of the founder of the Tecnimede Group, who always saw scientific research and internationalisation as strategic pillars. The award also reinforces Tecnimede Group’s commitment to fostering open innovation, aligned with its focus on value-added medicines and advanced therapies.